protein
Paired amphipathic helix protein Sin3a
Gene
SIN3A
Organism
Homo sapiens(9606)
Length
1273 aa
Mass
145,175 Da
SIN3A (Paired amphipathic helix protein Sin3a) is a transcriptional corepressor that functions as a histone deacetylase complex component (UniProt: Q96ST3). It regulates gene expression through interactions with multiple transcription factors including REST, MXI1, and MXD1-MAX heterodimers, and cooperates with OGT and FOXK1 in transcriptional repression. The protein plays roles in circadian rhythm control, cell cycle progression, and neuronal development.
SIN3A is expressed in cortical neurons where it is required for neuronal differentiation and callosal axon elongation. Mutations in SIN3A cause Witteveen-Kolk syndrome (WITKOS), an autosomal dominant neurodevelopmental disorder characterized by global developmental delay, intellectual disability, microcephaly, and distinctive facial dysmorphism, along with brain abnormalities including dilated ventricles and thin corpus callosum (UniProt: Q96ST3).
SIN3A is classified as a syndromic autism-associated gene (SFARI Cat 2), indicating evidence for involvement in autism spectrum disorder as part of its broader neurodevelopmental phenotype, though autism features are not the primary diagnostic hallmark of Witteveen-Kolk syndrome.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (By similarity). Required for cortical neuron differentiation and callosal axon elongation (By similarity)
Disease associations
Witteveen-Kolk syndromeWITKOS
An autosomal dominant syndrome characterized by global developmental delay, mild to severe intellectual disability, and facial dysmorphism. Additional features include short stature, microcephaly, joint hypermotility, and small hands and feet with digital abnormalities. Brain imaging shows dilated ventricles, thin corpus callosum and, in some cases, dysgyria or polymicrogyria.
Sources
Last updated 5/6/2026, 5:23:51 AM